Conformational difference between two types of biologically active oligodeoxynucleotides

Conformational difference between two types of biologically active oligodeoxynucleotides

Koji Umezawa1,2, Yoshinari Yamamoto3, Takeshi Shimosato1,2, Tomohide Takaya1,2.

  1. Graduate School of Science and Technology, Shinshu University.
  2. Institute for Biomedical Sciences, Shinshu University.
  3. Graduate School of Integrated Sciences for Life, Hiroshima University.

日本核酸医薬学会第5回年会 (大阪), 2019/07/10 (ポスター).


Single-stranded oligodeoxynucleotides (ODNs) show a particular biological activity depending on its nucleic-acid sequence. However, some of ODNs containing telomere sequence can show different biological activities. The 20-base ODN named as CpG-A-1585 controls an inflammatory response induced by platelet-activating factor. CpG-A-1585 contains a telomere sequence. Although the 18-base ODN named as myoDN contains the same telomere sequence as CpG-A-1585, myoDN does not affect immune function. myoDN induces differentiation of muscle myoblasts. Then, we focused on conformational difference between the two-type biologically active ODNs to reveal a functional conformation.

By using an enhanced sampling method, multicanonical molecular dynamics simulation, we obtained the simulated conformational ensembles of CpG-A-1585 and myoDN. We calculated probability of base-base contact within the molecule at 310K. The result of high-probability contact pattern indicated that the middle part of telomere sequence in CpG-A-1585 could preferably form a stacking structure while the last half of telomere sequence, guanine repeat, in myoDN preferred to adopt stacking. There was a difference in the first half of telomere sequence. These findings support the evaluation of the various biological activities of ODNs.